Disease-Modifying Therapy in Multiple Sclerosis: Evaluation of Patients Satisfaction in Iranian Multiple Sclerosis Population

Background: Medication satisfaction is a patient-reported outcome which could show medication adherence. The aim of this study was to determine Iranian MS patients’ satisfaction with Disease Modifying Therapies (DMTs). Methods: A standardized questionnaire was developed using Treatment Satisfaction Questionnaire for Medication (TSQM). The online link was released on IMSS (Iranian Multiple Sclerosis Society) social media channel, accessible to 4272 MS patients totally. Results: Three hundred and ninety-four patients participated in our survey with 324 females, 70 males and an F/M ratio of 4.6:1. The most frequent DMTs used were interferon-beta (IFNβ) followed by rituximab. The mean effectiveness and global satisfaction scores were significantly higher for injectable DMTs, while the convenience score was significantly higher for oral DMTs. Mean effectiveness and side-effect scores were significantly higher in the Tysabri group and convenience score was significantly higher in the fingolimod group while global satisfaction was higher in the IFNβ group. Conclusion: The global satisfaction and effectiveness were significantly higher with injectable DMTs while the convenience score was significantly higher with oral DMTs.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with an unpredictable course (1). A wide range of medications known as Disease Modifying Therapies (DMTs) have been approved for the treatment of MS in the recent decade. The balance between efficacy, side effects, and the long-term impact of treatment should be considered through the decision-making process of selection or switching DMTs (2). Higher adherence to prescribed DMTs enhances the level of disease control and may prevent relapse occurrence in MS patients (3). Factors affecting the level of treatment adherence include patient preference and satisfaction, convenience, side effects, and social and economic issues (4). Barbosa et al identified a significant association between the satisfaction of the treatment and compliance and persistence to that treatment (5). Medication satisfaction is a patient-reported outcome (PRO) that reflects the quality of pharmaceutical products and services and could be used as a screening tool for treatment adherence (6). Patient satisfaction with medication which includes items such as effectiveness, convenience, side effects, and global satisfaction provides information regarding the patient's perception of current treatment. Satisfaction is an important indicator of treatment adherence in patients (5). Iran is a high-risk zone of MS with an increasing incidence of MS in recent years and the number of patients increased dramatically (7). However, no studies have been performed to evaluate drug satisfaction and compare it among various DMTs in Iranian MS patients. So, we conducted this study to investigate MS patients' satisfaction with DMTs.

Results
Three hundred and ninety-four patients participated in our survey with 324 females, 70 males and an F/M ratio of 4.6:1. The most frequent DMT used were interferon-beta (IFNβ) followed by rituximab with the level of satisfaction with access to medications and post-marketing support services of 82% and 62% respectively (Table 1).  Table 2). The mean effectiveness and global satisfaction scores were significantly higher for injectable DMTs, while convenience score was significantly higher with oral DMTs (Table 3, figure 1, 4).
Mean effectiveness and side-effects scores were significantly higher in the Tysabri group (figure 1, 2) and convenience score was significantly higher in the fingolimod group, while global satisfaction was higher in the IFNβ group (Table 4, figure 3).

Discussion
TSQM is designed for assessing treatment satisfaction in chronic diseases such as arthritis, asthma, major depression, type I diabetes, hyperlipidemia, hypertension, migraine, psoriasis as well as MS ()10. Recent studies show that TSQM is useful to study treatment satisfaction with DMTs in patients with relapsing-remitting MS (RRMS) , and the results of the current study demonstrated that global satisfaction and effectiveness were significantly higher in the injectable DMTs group while convenience score was significantly higher in the oral DMTs group. In a previous study, Turčáni et al evaluated 417 MS patients and reported higher significant scores of global satisfaction and effectiveness in the infusion group while convenience was non-significantly higher in the oral group (4). They found significant higher global satisfaction and effectiveness scores in the Tysabri group, followed by fingolimod for effectiveness, and teriflunomide for global satisfaction. They reported that their patients were more convenient with teriflunomide followed by interferon beta-1b. Our results also show that global satisfaction was significantly higher in the IFNβ group followed by Dimethyl fumarate and Tysabri. We also found that effectiveness and side-effects scores were significantly higher in the Tysabri group, and convenience score was significantly higher in the fingolimod group.
In Glanz et al study, patients who were under treatment with Tysabri were more satisfied with the ability to treat or prevent the condition by their medication as well as being more convenient in comparison with IM IFNβ-1a (11). Oral medications have a higher convenience score which is expectable as they could be taken at home without hospitalization and consuming the time for infusion. In the TENERE study which was conducted by Vermersch et al (12), using TSQM; patient-reported level of satisfaction was higher with teriflunomide compared with injectable DMTs (IFNβ and GA) which is in agreement with Turčáni et al study (4). Hanson et al assessed satisfaction in MS patients receiving fingolimod (13) and reported the mean scores of convenience, effectiveness, and global satisfaction of 71.7, 70.1, and 68.9, respectively while mentioned scores were 89, 69, and 67 in our study. Fernández O conducted a study in Spain and evaluated medication satisfaction in MS cases who were under treatment with injectable DMTs and reported the mean scores of convenience, effectiveness and global satisfaction as 72.5, 66.8 and 68.8, respectively (14).
Since availability and costs of treatments, and physician preferences differ among nations, it is crucial to conduct national studies to evaluate medication satisfaction among patients of different countries. Tysabri is administered monthly and our results show that patient satisfaction regarding side-effects is better in Tysabri group when compared to other DMTs. The frequency of side effects plays an important role in determining the degree of medication satisfaction score. For instance, injection site reaction is common in subcutaneous IFNβ and is one of the main causes of switching DMTs in MS patients (15). This study had some limitations. First, it was a single center study. Second, we did not evaluate adherence simultaneously. Larger multi centric studies evaluating adherence and its association with satisfaction is In conclusion, the global satisfaction and effectiveness were significantly higher with injectable DMTs, while convenience score was significantly higher with oral DMTs.